RESUMO
Immune-mediated gastritis is a rare adverse effect in patients treated with immune checkpoint inhibitors. We present a patient with a diagnosis of cervical carcinoma under treatment with pembrolizumab who was admitted with nausea, vomiting and weight loss; an endoscopy revealed a ulcerated lesion covered by mucus in the antrum and gastric body. The biopsy revealed extensive denudation of the gastric mucosa with fibrin leukocyte reaction. Into the lamina propria, an increased lymphocytic and polymorphonuclear inflammatory infiltrate was observed. Immunohistochemistry confirmed positivity for PDL1 (clone SP2630) and combined positive score of 35%, with a relative contribution of epithelial cells of 25% and inflammatory cells of 10%. After three weeks with 30 mg meprednisone, a new endoscopy revealed a stomach with clear mucus content; fundus and body without lesions, and an antrum with congestive mucosa and multiple superficial ulcers covered by fibrin. Diagnostic and therapeutic aspects of immune-mediated gastritis are described.
La gastritis inmunomediada es un efecto adverso raro en pacientes bajo tratamiento con inhibidores del punto de control inmunitario; se presenta el caso de una paciente con carcinoma de cuello uterino bajo tratamiento con pembrolizumab que ingresa con náuseas, vómitos y pérdida de peso. La endoscopía demostró una lesión ulcerada cubierta por moco en antro y cuerpo gástrico. La biopsia reveló una extensa denudación de la mucosa gástrica con material fibrinoleucocitario. La lámina propia presentó incremento del infiltrado inflamatorio linfocitario y polimorfonuclear. La inmunohistoquímica confirmó positividad para PDL1 (clon SP2630) y un score positivo combinado (CPS) del 35%, con una contribución relativa de células epiteliales de 25% y de células inflamatorias de 10%. Luego de tres semanas de tratamiento con 30 mg de meprednisona, la endoscopía constató un estómago con contenido mucoso claro; fundus y cuerpo sin lesiones, antro con mucosa congestiva y múltiples úlceras extensas y superficiales cubiertas por fibrina. Se describen los aspectos diagnósticos y terapéuticos de la gastritis inmunomediada.
Assuntos
Gastrite , Humanos , Gastrite/induzido quimicamente , Gastrite/diagnóstico , Gastrite/tratamento farmacológico , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Fibrina/efeitos adversosRESUMO
Our objective is to determine the gastric regenerative effect of Petroselinum sativum L. (parsley) consumption in rats with ethanolinduced gastritis. We developed an analytical, experimental, classical, cross-sectional, prospective study. We worked with 36 male Wistar rats (250 ± 30 g.p.c.) randomly distributed into 6 groups (n=6). Groups II-VI were subjected to a 24-hour fast to induce gastric ulcer by administering 10 mL/kg.p.c. of 70% ethanol via orogastric. After one hour, group II was sacrificed to observe the ulcerative damage in the stomach. Afterward, the aqueous extract of fresh parsley leaves (EAHP) was prepared, and the following treatment was administered to the other groups through the orogastric route for 3 days: group III, 10 mL/kg.p.c. 0.9% NaCl solution; and EAHP to groups IV-VI (150, 300, and 600 mg/Kg.p.c., respectively). The rats were then fasted for 24 hours before being sacrificed by breaking their necks. Subsequently, a laparotomy was performed to extract the stomach. The EAHP generated greater production of gastric mucus in the doses of 300 mg/kg.p.c. with 78.03% and 600 mg/kg.p.c. with 80.52% (p<0.05). This was consistent with what was observed histologically in the gastric mucosa, showing only signs of inflammation of the submucosa in the groups that consumed EAHP (IV-VI), compared with fibrinoid necrosis in the groups that did not consume it (II and III). In conclusion, the consumption of EAHP has a gastric regenerative effect in rats with ethanol-induced gastritis.
Assuntos
Gastrite , Extratos Vegetais , Animais , Humanos , Masculino , Ratos , Antiulcerosos/uso terapêutico , Estudos Transversais , Etanol/toxicidade , Mucosa Gástrica/patologia , Gastrite/induzido quimicamente , Gastrite/patologia , Petroselinum , Extratos Vegetais/uso terapêutico , Estudos Prospectivos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológicoRESUMO
Galactomannans are neutral polysaccharides isolated from the endosperm of some Leguminosae seeds. They consist of a (1â¯ââ¯4) linked ß-mannopyranosyl backbone partially substituted at O-6 with α-d-galactopyranosyl side groups. C. pulcherrima have anti-inflammatory and muco-adhesive proprieties. Acute gastritis is an inflammatory disease triggered by use of non-steroidal anti-inflammatory drugs. We investigated the gastroprotective effect of galactomannan obtained from the seeds of Caesalpinia pulcherrima L. (GM-CP) in acute gastritis model induced by indomethacin. Gastritis was induced with indomethacin (30â¯mg/kg, P.·O.) in female Swiss mice. Animal groups (nâ¯=â¯7) were pretreated with saline-dissolved GM-CP (3â¯mg/kg, 10â¯mg/kg, 30â¯mg/kg, P.O.) or vehicle 1â¯h before gastritis induction. Mice were euthanized seven hours after the induction. The stomach and blood samples were collected for analysis. At 10â¯mg/kg, GP-CP reduced the extension of macroscopic lesion and the loss of superficial cells by alleviating inflammatory symptoms (neutrophil infiltration, migration and adhesion of mesenteric leukocytes, production of TNF-α and thiobarbituric acid reactive species (TBARS) and helping to maintain mucin labeling of the tissue. Thus, the findings of the study suggest that GM-CP exhibits gastroprotective effects.
Assuntos
Caesalpinia/química , Gastrite , Indometacina/efeitos adversos , Mananas/farmacologia , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Sementes/química , Doença Aguda , Animais , Feminino , Galactose/análogos & derivados , Gastrite/induzido quimicamente , Gastrite/metabolismo , Gastrite/patologia , Gastrite/prevenção & controle , Indometacina/farmacologia , Mananas/química , Camundongos , Neutrófilos/patologiaRESUMO
This study aimed to evaluate the effect of Lactobacillus reuteri DSM 17938 (DSM) on ethanol-induced gastric injury, and if its possible mechanism of action is related to inhibiting the transient receptor potential vanilloid type 1 (TRPV1). We evaluated the effect of supplementing 108 CFUâ¢g body wt-1â¢day-1 of DSM on ethanol-induced gastric injury. DSM significantly reduced the ulcer area (1.940 ± 1.121 mm²) with 3 days of pretreatment. The effects of DSM supplementation were reversed by Resiniferatoxin (RTX), TRPV1 agonist (3 nmol/kg p.o.). Substance P (SP) (1 µmol/L per 20 g) plus 50% ethanol resulted in hemorrhagic lesions, and DSM supplementation did not reverse the lesion area induced by administering SP. TRPV1 staining intensity was lower, SP, malondialdehyde (MDA) and nitrite levels were reduced, and restored normal levels of antioxidant parameters (glutathione and superoxide dismutase) in the gastric mucosa in mice treated with DSM. In conclusion, DSM exhibited gastroprotective activity through decreased expression of TRPV1 receptor and decreasing SP levels, with a consequent reduction of oxidative stress.
Assuntos
Etanol/efeitos adversos , Mucosa Gástrica/patologia , Limosilactobacillus reuteri/crescimento & desenvolvimento , Probióticos/uso terapêutico , Úlcera Gástrica/prevenção & controle , Substância P/antagonistas & inibidores , Canais de Cátion TRPV/antagonistas & inibidores , Animais , Antioxidantes/metabolismo , Diterpenos/farmacologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/induzido quimicamente , Gastrite/metabolismo , Gastrite/prevenção & controle , Glutationa/metabolismo , Limosilactobacillus reuteri/classificação , Malondialdeído/metabolismo , Camundongos , Substâncias Protetoras/uso terapêutico , Especificidade da Espécie , Estômago/microbiologia , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo , Canais de Cátion TRPV/farmacologiaRESUMO
BACKGROUND: In an increasing search for natural products that may heal the ulcers and avoid its recurrence, limonene appears as a promising candidate. HYPOTHESIS/PURPOSE: The present study aimed to investigate the protective effect of limonene in ethanol-induced gastric ulcers, in addition, to investigate the involvement of antioxidant and anti-inflammatory activities, besides the modulation of gene expression. STUDY DESIGN: Male Wistar rats were orally treated with vehicle (8% tween 80), carbenoxolone (100 mg/kg) or limonene (25, 50 or 100 mg/kg) and then orally received ethanol to induce gastric ulcers formation. METHODS: The activity of myeloperoxidase (MPO) was measured. Levels of glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD) were measured. We investigated the anti-inflammatory effect of limonene measuring the levels of pro-inflammatory cytokines tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and anti-inflammatory cytokine interleukin-10 (IL-10) by ELISA. Additionally, we investigate through real-time PCR (qPCR) the gene expression of nuclear factor-kappa B (Nf-κb), Gpx, Il-1ß, Mpo, and Il-10. RESULTS: Our results showed that limonene 50 mg/kg was the lowest effective dose, offering 93% of reduction in gastric ulcer area compared with the vehicle. There was an increase in mucus production and higher preservation of gastric mucosa integrity after treatment with limonene.There was a reduction in the MPO activity, a biomarker of neutrophils infiltration, and an increase in GPx activity, suggesting an antioxidant effect. Limonene displayed anti-inflammatory activity through decreasing the levels of TNF-a, IL-6, and IL-1ß and increasing the level of IL-10. Limonene could down-regulate the expression of Nf-κb, Il-1ß, and Mpo and up-regulate the expression of Gpx. CONCLUSION: Our results demonstrate that oral treatment with limonene exerts gastroprotection through local mucosal defense mechanisms, such as increasing the mucus production, modulation of the oxidative stress and inflammatory response and inhibition of Nf-κb expression.
Assuntos
Limoneno/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Úlcera Gástrica/prevenção & controle , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Etanol/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Gastrite/induzido quimicamente , Gastrite/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Limoneno/administração & dosagem , Masculino , Peroxidase/metabolismo , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/genética , Superóxido Dismutase/metabolismoAssuntos
Anemia , Transfusão de Sangue/métodos , Mucosa Gástrica , Gastrite , Hemorragia Gastrointestinal , Hemostasia Cirúrgica/métodos , Falência Renal Crônica/tratamento farmacológico , Sevelamer , Idoso , Anemia/diagnóstico , Anemia/etiologia , Anemia/terapia , Quelantes/administração & dosagem , Quelantes/efeitos adversos , Diagnóstico Diferencial , Endoscopia do Sistema Digestório/métodos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Gastrite/induzido quimicamente , Gastrite/complicações , Gastrite/patologia , Gastrite/terapia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/fisiopatologia , Hemorragia Gastrointestinal/cirurgia , Humanos , Falência Renal Crônica/terapia , Masculino , Sevelamer/administração & dosagem , Sevelamer/efeitos adversos , Resultado do Tratamento , Suspensão de TratamentoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Barks of Ximenia americana are used by the population to treat gastrointestinal inflammatory disorders. Indomethacin is a non-selective non-steroidal anti-inflammatory drug that induces marked gastrointestinal damage. AIMS OF THE STUDIES: To evaluate the gastroprotective activity of total polysaccharides contained in the extract (TPL-Xa) or tea (Tea-Xa) of Ximenia americana barks in the mice gastric damage induced by indomethacin. MATERIALS AND METHODS: TPL-Xa was obtained by a combination of NaOH extraction and ethanol precipitation. Tea-Xa was prepared in distilled water boiled during 5â¯min. Animals received p.o. 0.9% NaCl (saline - control group), TPL-Xa (1-90â¯mg/kg) or Tea-Xa 1â¯h before gastritis induction by indomethacin (20â¯mg/kg). Mice were sacrificed 7â¯h after gastritis induction and analyzed for the following parameters: stomach lesions measurement; histological evaluation; myeloperoxidase (MPO) activity; nitrate/nitrite and cytokine levels; leukocyte adhesion and rolling by intravital microscopy. RESULTS: TPL-Xa reduced macroscopic and microscopic damage, MPO activity (59%), leukocyte rolling (86%) and adhesion (84%), nitrite/nitrate ratio (100%) and IL-8 (69%), but increased IL-4 (50%). Tea-Xa (12.8 yield; 39.3% carbohydrate, including 25.8% uronic acid; 4% protein) reduced macroscopic damage (62%) and MPO activity (50%). CONCLUSION: TPL and Tea of Ximenia americana barks ameliorate the gastric injury induced by indomethacin in mice, an effect that was dependent on the reduction of neutrophil infiltration.
Assuntos
Bebidas , Gastrite/tratamento farmacológico , Olacaceae , Extratos Vegetais , Polissacarídeos , Substâncias Protetoras , Animais , Anti-Inflamatórios não Esteroides , Adesão Celular/efeitos dos fármacos , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite/induzido quimicamente , Gastrite/imunologia , Gastrite/metabolismo , Indometacina , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Migração e Rolagem de Leucócitos/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Leucócitos/fisiologia , Camundongos , Infiltração de Neutrófilos/efeitos dos fármacos , Nitratos/metabolismo , Nitritos/metabolismo , Peroxidase/metabolismo , Fitoterapia , Casca de Planta , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêuticoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The leaves from Vernonia condensata Baker are broadly used in folk medicine for the treatment of gastric ulcers and dyspepsia. The Brazilian Public Health System (SUS) describes this species as having the potential to serve as a new herbal product with therapeutic benefits. AIM OF THE STUDY: The purpose of the study was to evaluate the gastroprotective activity and gastric healing properties of a crude ethanolic extract from leaves of V. condensata (CEEV) in different animal models. MATERIALS AND METHODS: In order to assess the gastroprotective potential of CEEV, ulcer models were established using ethanol and indomethacin. The gastric healing effect was then evaluated in the acetic acid-induced ulcer model, where the tissue was used to assess oxidative levels (reduced glutathione and lipid hydroperoxide levels, as well as superoxide dismutase and catalase activity), inflammatory [myeloperoxidase (MPO)] parameters, and mucin content. Furthermore, the ligature pylorus model, with and without secretagogue stimuli, was employed to investigate the mechanism of action of CEEV. In addition, H(+)K(+)-ATPase activity, MPO activity, and antioxidant activity through the DPPH assay were examined through in vitro trials. Phytochemical analyses were also performed. The ethanol/HCl-induced gastric ulcer method was employed to verify the gastroprotective effect of the main compound in CEEV. RESULTS: CEEV (30 and 300mg/kg, p.o) exhibited gastroprotective activity and prevented both gastric lesions induced by ethanol or indomethacin in rats. The gastric healing effect of CEEV (300mg/kg, p.o. taken twice a day for a duration of seven days) was confirmed by examining the macroscopic and microscopic appearance of chronic gastric ulcers induced by acetic acid in rats. The restorative effect of CEEV was accompanied by a significant increase in mucin content (PAS staining) and by a reduction in oxidative stress and inflammatory parameters at the site of the ulcer. Moreover, CEEV (300mg/kg), administered via an intraduodenal route, significantly reduced the volume, pH, total acidity and pepsin activity of gastric content in the pylorus ligature model in rats. The gastric acid antisecretory effect of CEEV was maintained even in the presence of cholinergic and gastrinergic, but not histaminergic, stimuli. In vitro, CEEV (1-10µg/ml) was able to scavenge free radical DPPH, but did not promote inhibitory effects on MPO or H(+),K(+)-ATPAse activity. Phytochemical analysis of CEEV indicated that luteolin is the main compound present in the extract. However, luteolin (1, 3 and 10mg/kg, p.o or 1mg/kg, i.p.) did not promote gastroprotection against ethanol/HCl in mice. It is also important to mention that oral administration of CEEV did not produce any sign of acute toxicity in animals. CONCLUSIONS: V. condensata extract demonstrates gastroprotective effects through the inhibition of gastric secretion via cholinergic and gastrinergic pathways. Furthermore, it exhibits cytoprotective effects, involving antioxidant activity, an increase in mucin content and inhibition of neutrophil migration. Thus, this medicinal plant may be a suitable natural source for the prevention and treatment of gastric lesions.
Assuntos
Antiulcerosos , Gastrite/tratamento farmacológico , Extratos Vegetais , Úlcera Gástrica/tratamento farmacológico , Vernonia , Animais , Antiulcerosos/química , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Catalase/metabolismo , Etanol , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite/induzido quimicamente , Gastrite/metabolismo , Gastrite/patologia , Glutationa/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Indometacina , Camundongos , Mucinas/metabolismo , Peroxidase/metabolismo , Fenóis/análise , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Plantas Medicinais , Coelhos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismoRESUMO
Oral transmission of the protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas disease, has been documented in Latin American countries. The reported cases of infection were due to the ingestion of contaminated fresh fruit, juices, or sugar cane juice. There have been few studies on the physiopathology of the disease in oral transmission cases. Gastritis is a common ailment that can be caused by poor dietary habits, intake of alcohol or other gastric irritants, bacterial infection, or by the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated in a mouse model whether gastric mucosal injury, induced by aspirin, would affect the course of disease in animals infected with T. cruzi by the oral route. The CL14 and G strains of T. cruzi, both of low infectivity, were used. To this end, groups of BALB/c mice were treated during 5 days with aspirin (100 mg kg(-1)) before oral infection with T. cruzi metacyclic forms (4 × 10(5) or 5 × 10(7) parasites/mouse). Histological analysis and determination of nitric oxide and TNF-α were performed in gastric samples obtained 5 days after infection. Parasitemia was monitored from the thirteenth day after infection. The results indicate that aspirin treatment of mice injured their gastric mucosa and facilitated invasion by both CL14 and G strains of T. cruzi. Strain CL14 caused more severe infection compared to the G strain, as larger numbers of amastigote nests were found in the stomach and parasitemia levels were higher. Our study is novel in that it shows that gastric mucosal damage caused by aspirin, a commonly used NSAID, facilitates T. cruzi infection by the oral route.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Doença de Chagas/etiologia , Mucosa Gástrica/efeitos dos fármacos , Gastrite/complicações , Animais , Bebidas/parasitologia , Doença de Chagas/transmissão , Carboidratos da Dieta , Feminino , Parasitologia de Alimentos , Frutas/parasitologia , Mucosa Gástrica/química , Mucosa Gástrica/patologia , Gastrite/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nitritos/metabolismo , Estômago/parasitologia , Trypanosoma cruzi/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
INTRODUCTION: There is no clear consensus on the management of accidental ingestion of caustic substances in paediatrics. The aim of this study was to determine the profile of the paediatric population treated due to caustic ingestion in a Healthcare Centre. PATIENTS AND METHOD: A descriptive study was conducted on patients treated for the ingestion of caustic substances in our hospital during the period 2008-2011. RESULTS: A total of 12 patients were treated, with a mean age of 3.8 years (1-13 years), with the majority males (58.8%). An alkaline product was ingested by 58.3%, and an acid by 41.6%. The majority (58.3%) did not refer to symptoms and the remainder referred to vomiting (33.3%), odynophagia (16.6%), haematemesis (8.3%), hyper-salivation (8.3%) and shortness of breath (8.3%). Oral cavity lesions were observed in 75% of cases. All, except one, were accidental. An endoscopy was performed on all of them (100%) between 12 and 24hours post-ingestion, with pathological findings in 41.6%. In the group that ingested an alkali, 2 (16.6%) patients had lesions, one a grade 2B and one a grade 3 oesophagitis. In the acid ingestion group, 4 (33.3%) patients had lesions; one grade 1-2A oesophagitis, two acute non-erosive gastritis, and one acute haemorrhagic gastritis. A follow-up endoscopy was performed depending on the previous endoscopic findings. Only two patients presented with complications. CONCLUSIONS: Emphasis is placed on the endoscopic evaluation in the first 24hours of deliberate asymptomatic ingestions, as well as a strict follow-up in those that ingested acids, due to delayed associated lesions.